The evolution of multicellular organisms is dependent upon the ability of cells to communicate with each other and with their environment. One method the cells use for this communication is to release peptides that induce a specific activity in the receiving cell.
Such a peptide with biological activity is the human plasma growth factor copper-binding tripeptide glycyl-L-histidyl-L-lysine (GHK--Cu.sup.2+).
L Pickart and S Lovejoy describe the properties of the peptide GHK--Cu.sup.2+ in Methods in Enzymology, Vol 147 (1987) pp 314-328, Academic Press. It plays a physio-logical role in the healing of wounds by stimulation of the complex course of events necessary for the formation of new tissues such as angiogenesis and axon and dendrite growth in neurons. The peptide has also a chemoattractive effect on cells necessary for wound-healing such as macrophages, monocytes, mast cells and capillary endothelial cells.
Collagen is a fibrous protein that constitutes a quarter of the total amount of protein in the human body. It is the major fibrous element of skin, bone, tendons, cartilage, ligaments and blood vessels. Collagen is synthesized by fibroblasts, a type of cell localized in the area surrounding other cells and tissues.
In a publication in FEBS Letters 238 (1988) 343-346, F--X Maquart et al present data showing that GHK--Cu.sup.2+ stimulates collagen synthesis in cultures of fibroblasts. This stimulation is observed at a peptide concentration as low as 10.sup.-12 M and reaches a maximum at 10.sup.-9 M where the increase in collagen synthesis is about 80%.
In European Patent Appliction 0190736, GHK--Cu.sup.2+ with a modified C-terminal carboxyl group is used as an ointment for faster healing of wounds.
GHK--Cu.sup.2+ possesses a significant superoxide dismutase-like activity with a rate constant of about 25% of the activity of enzymatic Cu,Zn-superoxide dismutase on a molar basis. When wounds and damaged tissue are present, cells from the immune system invade the injured area and large quantities of toxic oxygen radicals are released to kill invading bacteria. These radicals also destroy intact tissue which starts a vicious circle where more radicals are released, thus delaying healing. GHK--Cu.sup.2+ superoxide dismutase activity detoxifies the tissue destroying superoxide anions.
Aggregation of blood platelets is the first stage of thrombosis. GHK--Cu.sup.2+ inhibits this aggregation and it also inhibits the hormone thromboxane which causes thrombosis.
The structure of the tripeptide GHK--Cu.sup.2+ is shown in FIG. 1. The affinity of the peptide for copper is very high with a pK for the dissociation constant of about 16. For biological activity the .epsilon.-amino group on the side-chain of the lysine must be free.